Arterial blood gas and pH values are of primary importance in the management of critical care and surgical patients. The three parameters of interest are the partial pressures of oxygen (PO.sub.2) and carbon dioxide (PCO.sub.2), and the negative logarithm of hydrogen ion activity (pH). These three parameters are a good indication of a patient's cardiac, respiratory and circulatory functioning.
The standard technique for measuring blood gases involves invasive sampling from the radial artery, with analysis of the blood sample conducted in a diagnostic laboratory, usually some distance from the patient. The results are typically obtained 10-20 minutes after the sample has been taken, during which time the patient's blood gas levels may have changed.
This lack of timely results and the use of single-point sampling are problems which make it difficult to determine current patient status and to recognize trends. Also, there is a source of potential error resulting from the extensive sample handling from bedside to laboratory. The desire for improved patient care by eliminating these drawbacks has created the need for an improved blood gas monitoring system.
Among the suggested improvements is a continuous blood gas monitoring system utilizing an invasive probe placed directly in an artery having electrical or optical sensing means. The in vivo electrode probes have not been generally accepted because of the danger of using electrical currents in the body and the difficulty of properly calibrating the electrodes.
In a fiber optic system, light from a suitable source travels along an optically conducting fiber to its distal end where it undergoes some change caused by interaction with a component of the blood to be measured, or interaction with a material contained in the probe tip which is sensitive to the component of the blood, and the modified light returns along the same or another fiber to a light-measuring instrument which interprets the return light signal. This system offers several potential benefits. A fiber optic sensor is safe, involving no electrical currents in the body. Optical fibers are very small and flexible, allowing placement in the very small blood vessels of the body. The materials used, i.e., plastic, metal and glass, are suitable for long-term implantation. However, although the potential benefits of an indwelling fiber optic blood gas sensor have long been recognized, they have not yet been realized in the viable commercial product.
Optical blood gas sensors based on fluorescent dyes are described in J. Gehrich et al., "Optical Fluorescence And Its Application To An Intravascular Blood Gas Monitoring System," IEEE Transactions On Biomedical Engineering, Vol. BME-33, No. 2, February 1986, pp. 117-132. Fluorescence is a type of photo-luminescence in which light energy is emitted when an electron returns from an excited singlet state to the ground state. Phosphorescence is a longer-lived type of photoluminescence in which the release of energy is from the triplet state. Because fluorescent and phosphorescent dyes emit light energy at a wavelength different from that at which they absorb the excitation energy, a single optical fiber can be used to both deliver and receive light energy from the sensor dye. Use of the single fiber reduces the diameter of the sensor probe, an important consideration in enabling placement of the sensors in an artery or vein. A blood oxygen sensor based on a phosphorescent lanthanide complex is described in U.S. Pat. No. 4,861,727 to Hauenstein et al. Hauenstein et al. describes an oxygen-quenchable luminescent lanthanide complex disposed in a solid polymeric matrix at the distal end of an optical fiber. A non-oxygen quenchable reference complex is also provided to continuously monitor the source radiation and losses in the sensor system.
Another type of optical sensor is based on the principle of optical absorption. In this case, a sensor disposed in the blood is permeated by the component of interest and an optical signal passing through the sensor is absorbed by the component in direct proportion to the concentration of the component, such that the energy signal which exits the sensor is reduced in an amount proportional to the concentration of the component in the blood. A carbon dioxide (CO.sub.2) sensor of this type is described in U.S. Pat. No. 4,800,886 to Nestor in which a fixed-length axial segment is provided at the end of an optical fiber, which segment is permeable to CO.sub.2.
The challenges in designing a fiber optic blood gas sensor include the selection of a sensing material which has the proper absorption and emission wavelength characteristics, is non-toxic, is capable of attachment to an optical fiber (or to a suitable matrix), and has sufficient intensity (signal strength) and sufficient intensity variation over the physiological measurement range (sensitivity and range) to adequately follow physiological changes of the blood gas parameters. The sensing material must also not be affected by drugs or blood components, and must be stable enough to maintain accuracy for up to three days (72 hours) of use. Furthermore, since it is desirable to provide a disposable product, consideration must be also be given to the cost and shelf life.
A principal difficulty with the invasive blood gas systems currently under development concerns the time-consuming, costly and error-prone calibration process required just prior to use. As described in C. Mahutte, et al., "Progress In The Development Of A Fluorescent Intravascular Blood Gas System In Man," Journal of Clinical Monitoring, Vol. 6, No. 2, April 1990, pp. 147-157, the sensors now under development require a 20-minute calibration procedure which is done at the patient's bedside just prior to use. During calibration, the sensor is placed in at least two buffered solutions, each containing different precisely known concentrations of oxygen and carbon dioxide. Based on the sensor response to these standard solutions, calibration constants are determined which enable conversion of the measured intensity to an actual blood gas value by accounting for the bias between the measured and actual values and a temperature correction (in that CO.sub.2 and O.sub.2 measurements are both temperature dependent).
There are a number of problems with the standard calibration technique. The calibration solutions must be highly uniform to provide consistent results. The solutions are typically unstable and thus are prepared only as needed or prepackaged in glass ampules. The ampules require careful handling during the calibration process to avoid breakage. Shelf life problems, i.e., change of chemistry, separation, etc., may be encountered with prepackaged solutions that are stored over a period of time. There is a danger of contamination. The calibration equipment is cumbersome and costly, including two glass bottles, each with different but precisely controlled values of oxygen and carbon dioxide, tubing, pressure regulators, flow restrictors and solenoid valving as necessary to select the desired gas mixtures and control the flow within required ranges. Trained personnel are generally required to perform this procedure at the bedside. The calibration accuracy depends upon the strictness to which the calibration protocol is followed. Requiring this procedure at the patient's bedside, as opposed to in the factory where the product is manufactured, increases the likelihood of errors being made in the calibration procedure.
If the calibratable device is to be stored over a period of time, the device is most easily stored in the dry state to avoid problems arising from the storage of a moist device. In particular, the dry state is far more amenable to the requirement that the device be rendered sterile and held in a sterile state throughout its useful life. However, bringing the sensing component of the device from a dry to an equilibriated wet state often requires hydrating the sensor over an extended period of time. While it has been suggested to sell the sensor packaged in a calibration cuvette which contains the calibration solution (see J. Gehrich et al. at p. 124, and C. Mahutte et al. at p. 149), this leads to rather elaborate and expensive packaging techniques and does not eliminate the need for a bedside calibration.
Finally, it is generally required with the known devices that calibration be done just prior to placement in the patient, which means within a few minutes. Thus, if some unexpected delay is encountered, the entire calibration procedure may have to be redone. Further, calibration just prior to placement may jeopardize device sterility and requires that the calibration be performed in a sterile environment. Also, after placement in the patient, the known devices may only be stable for less than 24 hours, before requiring recalibration. It would be desirable to have a device remain stable up to 72 hours after placement.
It is an object of the present invention to provide an optical sensor which can be calibrated in the factory prior to shipment to the customer, and which does not require recalibration prior to use.
A further object is to provide a precalibrated sensor which can be stored in a dry condition, and does not require packaging and storage in a calibration solution.
A still further object is to provide a sensor which can be calibrated and then sterilized, wherein the sterilization procedure does not substantially effect the calibration.